1. Field of the Invention
The present invention relates to a monoester of malonic acid and a process for producing the same.
2. Related Art
Carbapenem antibacterial agents have potent antibacterial activity against a wide spectrum of Gram-positive bacteria and Gram-negative bacteria. Up to now, for example, Imipenem, Meropenem, and Biapenem have been developed as carbapenem antibacterial agents for clinical administration as injections. For example, when a strain on patients is taken into consideration, however, oral carbapenem antibacterial agents are clinically highly useful because they can be simply and easily administered and administration at home is possible. For this reason, several orally administrable carbapenem antibacterial agents have hitherto been examined (for example, Japanese Patent Publication No. 2666118).
Monoesters of malonic acid are promising compounds which can be intermediates important to the production of a number of orally administrable carbapenem antibacterial agents (for example, Japanese Patent Laid-Open Publication Nos. 123985/1981, 255280/1988, and 284176/1988).
However, it should be noted that an ester group as a protective group of a carboxyl group in the monoester of malonic acid used in the conventional production process of carbapenem antibacterial agents is a substituent that cannot easily be removed by hydrolysis in vivo (for example, a p-nitrobenzyl ester group). In the prior art technique, a contemplated prodrug-type carbapenem antibacterial agent for oral administration is produced by converting the monoester of malonic acid with this protective group to a predetermined intermediate, then removing the ester group as the protective group derived from the monoester of malonic acid (deprotection step), and further converting that part to an ester group that can easily be hydrolyzed in vivo (prodrug preparation step).
As far as the present inventors know, up to now, the use of a group, which can easily be hydrolyzed and removed in vivo, as an ester group which is the protective group of the carboxyl group in the monoester of malonic acid used in the production process of carbapenem antibacterial agents has not been known. Further, specific compounds of the monoester of malonic acid with the above ester group, and the production process and property data of such compounds have not hitherto been disclosed.